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CAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies

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  • Yongxian Hu

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Jingjing Li

    (The First Affiliated Hospital, Zhejiang University School of Medicine
    Zhejiang University)

  • Fang Ni

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Zhongli Yang

    (The First Affiliated Hospital, Zhejiang University School of Medicine
    Zhejiang University)

  • Xiaohua Gui

    (The First Affiliated Hospital, Zhejiang University School of Medicine
    Zhejiang University)

  • Zhiwei Bao

    (The First Affiliated Hospital, Zhejiang University School of Medicine
    Zhejiang University)

  • Houli Zhao

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Guoqing Wei

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Yiyun Wang

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Mingming Zhang

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Ruimin Hong

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Linqin Wang

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Wenjun Wu

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

  • Mohamad Mohty

    (Hospital Saint Antoine
    INSERM UMRs 938, and EBMT Paris Study office/CEREST-TC)

  • Arnon Nagler

    (Chaim Sheba Medical Center)

  • Alex H. Chang

    (Tongji University School of Medicine)

  • Marcel R. M. Brink

    (Memorial Sloan Kettering Cancer Center)

  • Ming D. Li

    (The First Affiliated Hospital, Zhejiang University School of Medicine
    Zhejiang University)

  • He Huang

    (Zhejiang University
    Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy
    Zhejiang University
    Zhejiang University Medical Center)

Abstract

Immunotherapy utilizing chimeric antigen receptor T cell (CAR-T) therapy holds promise for hematologic malignancies, however, response rates and associated immune-related adverse effects widely vary among patients. Here we show, by comparing diversity and composition of the gut microbiome during different CAR-T therapeutic phases in the clinical trial ChiCTR1800017404, that the gut flora characteristically differs among patients and according to treatment stages, and might also reflect patient response to therapy in relapsed/refractory multiple myeloma (MM; n = 43), acute lympholastic leukemia (ALL; n = 23) and non-Hodgkin lymphoma (NHL; n = 12). We observe significant temporal differences in diversity and abundance of Bifidobacterium, Prevotella, Sutterella, and Collinsella between MM patients in complete remission (n = 24) and those in partial remission (n = 11). Furthermore, we find that patients with severe cytokine release syndrome present with higher abundance of Bifidobacterium, Leuconostoc, Stenotrophomonas, and Staphylococcus, which is reproducible in an independent cohort of 38 MM patients. This study has important implications for understanding the biological role of the microbiome in CAR-T treatment responsiveness of hematologic malignancy patients, and may guide therapeutic intervention to increase efficacy. The success rate of CAR-T cell therapy is high in blood cancers, yet individual patient characteristics might reduce therapeutic benefit. Here we show that therapeutic response in MM, ALL and NHL, and occurrence of severe cytokine release syndrome in multiple myeloma are associated with specific gut microbiome alterations.

Suggested Citation

  • Yongxian Hu & Jingjing Li & Fang Ni & Zhongli Yang & Xiaohua Gui & Zhiwei Bao & Houli Zhao & Guoqing Wei & Yiyun Wang & Mingming Zhang & Ruimin Hong & Linqin Wang & Wenjun Wu & Mohamad Mohty & Arnon N, 2022. "CAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32960-3
    DOI: 10.1038/s41467-022-32960-3
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    References listed on IDEAS

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    1. Nan Xiao & Meng Nie & Huanhuan Pang & Bohong Wang & Jieli Hu & Xiangjun Meng & Ke Li & Xiaorong Ran & Quanxin Long & Haijun Deng & Na Chen & Shao Li & Ni Tang & Ailong Huang & Zeping Hu, 2021. "Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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